1-Acyl-4-substituted phenyl thiosemicarbazides

ABSTRACT

A novel process for the preparation of s-triazolo[3,4-b]benzothiazole compounds comprises reacting a molar equivalent of base in an amide solvent at a temperature from 60° C. to 200° C. with (a) a 1-acyl-4-(o-halophenyl)thiosemicarbazide compound or (b) a 4-(o-halophenyl)-1,2,4-triazole-3-thiol compound and recovering the product. The s-triazolo[3,4-b]benzothiazole compounds are useful for the control of plant pathogens.

This is a division of application Ser. No. 739,158, filed Nov. 5, 1976and issued Apr. 4, 1978, as U.S. Pat. No. 4,082,762. Application Ser.No. 739,158 is a division of application Ser. No. 607,848 filed Aug. 25,1975 and issued Feb. 15, 1977 as U.S. Pat. No. 4,008,242. ApplicationSer. No. 607,848 is, in turn, a division of application Ser. No. 449,141filed Mar. 7, 1974 and issued Feb. 10, 1976 as U.S. Pat. No. 3,937,713.

BACKGROUND OF THE INVENTION

Certain substituted s-triazolo[3,4-b]benzothiazoles (hereinafterreferred to as "triazolobenzothiazole compounds") are employed for thecontrol of plant pathogens, including fungal organisms and bacterialorganisms. Thus, the triazolobenzothiazole compounds can be employed forthe control of such organisms as crown gall, rice blast, leaf rust,powdery mildew, anthracnose, and the like. The compounds areparticularly suited for the control of fungal organisms, and giveparticularly good results in the control of rice blast. Belgium Pat. No.789,918 describes their preparation by cyclodehydration of2-acylhydrazinobenzothiazole compounds with polyphosphoric acid.

It is a purpose of this invention to provide a novel process for thepreparation of triazolobenzothiazole compounds, useful as plantfungicides, and in addition to provide new intermediate1-acyl-4-(o-halophenyl)thiosemicarbazide compounds and4-(o-halophenyl)-1,2,4-triazole-3-thiol compounds which are utilized inthe preparation of such triazolobenzothiazole compounds.

SUMMARY OF THE INVENTION

This invention relates to a novel process for the preparation ofs-triazolo[3,4-b]benzothiazole compounds represented by the formula##STR1## which comprises commingling at least a molar equivalent of basein a substantially anhydrous amide solvent at a temperature from about60° C. to about 200° C. with (a) an equimolar mixture of anacylhydrazine of the formula ##STR2## and an o-halophenylisothiocyanateof the formula ##STR3## which has been maintained a temperature of about60° C. to about 100° C. for about 24 hours; or (b) a1-acyl-4-(o-halophenyl)thiosemicarbazide of the formula ##STR4## or (c)a 4-(o-halophenyl)-1,2,4-triazole-3-thiol of the formula ##STR5## andrecovering the product; wherein, in the foregoing formulae, R ishydrogen, C₁ -C₁₁ alkyl, cyclopropyl or trifluoromethyl; R₁ is hydrogen,bromo, chloro or fluoro; R₂ and R₃ are independently hydrogen, C₁ -C₃alkyl, C₁ -C₃ alkoxy, bromo, chloro, fluoro or trifluoromethyl with thelimitation that at least one of R₂ and R₃ is hydrogen; X is bromo,chloro or fluoro; and subject to the further limitations that when R₁ ishalogen, R is other than hydrogen and R₂ is hydrogen.

In addition this invention is concerned with the preparation of thenovel intermediate 1-acyl-4-(o-halophenyl)-3-thiosemicarbazide and the4-(o-halophenyl)-1,2,4-triazole-3-thiol compounds which are used toprepare the triazolobenzothiazole plant fungicides.

DETAILED DESCRIPTION OF THE INVENTION

This invention relates to a novel process for the preparation ofs-triazolo[3,4-b]benzothiazole compounds represented by the formula##STR6## wherein R is hydrogen, C₁ -C₁₁ alkyl, cyclopropyl ortrifluoromethyl;

R₁ is hydrogen, bromo, chloro or fluoro;

R₂ and R₃ are independently hydrogen, C₁ -C₃ alkyl, C₁ -C₃ alkoxy,bromo, chloro, fluoro or trifluoromethyl with the limitation that atleast one of R₂ and R₃ is hydrogen;

subject to the further limitations that when R₁ is halogen, R is otherthan hydrogen and R₂ is hydrogen; which comprises commingling a molarequivalent of base in a substantially anhydrous amide solvent at atemperature from about 60° C. to about 200° C. with

a. a 1-acyl-4-(o-halophenyl)-3-thiosemicarbazide compound; or

b. a 4-(o-halophenyl)-1,2,4-triazole-3-thiol compound; and recoveringthe product.

The term "C₁ -C₁₁ alkyl" represents branched or straight-chain alkylgroups of from 1 to 11 carbon atoms. Exemplary of such straight-chainalkyl groups are methyl, propyl, pentyl, hexyl, octyl, decyl, and thelike. Exemplary of the branched chain alkyl groups are isopropyl,t-butyl, isopentyl, neopentyl, isohexyl, 3-methylpentyl,2,3,5-trimethylhexyl, 2,5-dimethyl-4-ethylheptane and the like. The term"C₁ -C₃ alkyl" includes methyl, ethyl, propyl and isopropyl. The term"C₁ -C₃ alkoxy" represents ether groups such as methoxy, ethoxy,propoxy, and isopropoxy. Where the term "halo" or "halogen" is employed,it refers to bromine, chlorine and fluorine only.

In addition, this invention is concerned with the preparation of theuseful intermediate 1-acyl-4-(o-halophenyl)-3-thiosemicarbazidecompounds, represented by the formula ##STR7## and the4-(o-halophenyl)-5-substituted-1,2,4-triazole-3-thiol compounds,represented by the formula ##STR8## wherein R, R₁, R₂, R₃ and X are asdefined hereinabove. These novel intermediate compounds are utilized inthe process of the present invention by reaction with a molar equivalentof base in a substantially anhydrous amide solvent.

All the starting materials and intermediates required in the instantprocess are prepared by methods known to the art. The 1-acylhydrazinecompounds represented by the formula ##STR9## are prepared by reactinghydrazine with the appropriate acid derivatives such as the acidchloride, the anhydride or the ester. [see Organic Reactions, Vol. 3,N.Y., Wiley, 1946, pp. 366-369].

The o-halophenylisothiocyanate compounds represented by the formula##STR10## are prepared by reacting the appropriate o-haloanilines withdimethylaminothiocarbamoyl chloride in an aromatic solvent [see J. Org.Chem., 30, 2465 (1965)].

The intermediate 1-acyl-4-(o-halophenyl)-3-thiosemicarbazide compounds,are prepared by reacting the aforementioned starting materials in anaprotic solvent at elevated temperatures. The thiosemicarbazides in turnare converted to the triazolothiol compounds by reaction with aqueousbase, as described in Ind. J. Chem., 5(9), 397 (1967); Chem. Abst. 68,59501w (1968). The reaction sequence leading to the triazolothiolcompounds is outlined below. ##STR11## After initial thiosemicarbazideformation a double intramolecular cyclization is effected to produce thebenzothiazole: (1) a cyclodehydration to provide the triazolothiol and(2) an aromatic halogen displacement to provide the desiredbenzothiazole compound. The cyclodehydration provides a4-(o-halophenyl)-1,2,4-triazole-3-thiol which undergoes aromatic halogendisplacement by thiol anion generated in the presence of base to providethe instant triazolobenzothiazole compound.

In the halogen displacement reaction by thiol anion, R₁ is equivalent toX when both are bromo, chloro or fluoro. One of R₁ or X is displaced toprovide a 5-bromo-, 5-chloro- or 5-fluorotriazolobenzothiazole. When R₁and X are separately bromo, chloro or fluoro, mixtures of 5-chloro-,5-bromo- and 5-fluorotriazolobenzothiazoles are obtained. Such mixturesare separable by methods such as fractional crystallization orchromatography. The process operates when R₁ or X is iodo; however, therequired o-iodophenylisothiocyanate starting materials are less readilyavailable. They are more difficult to prepare and render the processless economical.

In general, it appears that electronegative phenyl substituentsfacilitate halogen displacement as evidenced by high product yields andshort reaction times. Electron donating substituents such as methyl tendto retard halogen displacement resulting in increased reaction times andproduction of dimeric side products.

The 1-acyl-4-(o-halophenyl)-3-thiosemicarbazide compounds are preparedby reacting molar equivalents of an acylhydrazine compound and ano-halophenylisothiocyanate in a substantially anhydrous aprotic solventat a temperature from about 60° C. to about 100° C. for about 24 hours.A substantially anhydrous aprotic solvent refers to a type of solventwhich does not offer or accept protons but which might possibly stillcontain trace amounts of water. Exemplary of the aprotic solventsemployed are benzene, dichloroethane, dioxane, the dimethylether ofethylene glycol, tetrahydrofuran (THF), and the like. THF is a preferredsolvent for the preparation of the thiosemicarbazide compounds. Thethiosemicarbazide product is recovered by evaporation of the solvent andpurified by conventiona methods.

The 4-(o-halophenyl)-5-substituted-1,2,4-triazole-3-thiol compounds areprepared from the corresponding thiosemicarbazide compounds bycyclodehydration with a molar equivalent of an alkali metal hydroxide inan aqueous or dilute C₁ -C₃ carbinol medium. Exemplary of suitablecarbinol solvents are methanol, ethanol, propanol and isopropanol. Thepreferred cyclodehydration conditions are aqueous sodium hydroxide andsteam bath temperature. If desired, the triazolothiol salt can beobtained by evaporation of the solvent and heated in an amide solvent toprovide the triazolobenzothiazole compounds. Usually, however, the basicmixture is acidified and the insoluble triazolothiol compound isrecovered for use in the process.

It will be noted that it is not necessary to isolate the intermediatethiosemicarbazides or triazolothiols to operate the process.

Solvents which may be employed in the instant process are commonly usedtertiary amide solvents, which are unreactive with the startingmaterials and product. A substantially anhydrous tertiary amide solventcan be used. The term "substantially anhydrous" means that the presenceof small amounts of water can be tolerated in the solvent. Generally theamide solvent can be "dried" in situ by using 1 to 10 percent excess ofbase to react with the residual water. Exemplary of the amide solventswhich are employed are N,N-dibutylacetamide, dimethylacetamide (DMAC),dimethylformamide (DMF), N-methyl-2-pyrrolidone, and the like. Thehigher amide solvents are effective because of their higher boilingtemperatures. For reasons of availability and ease of removal, DMAC andDMF are preferred solvents.

In general, any base which is strong enough to generate a triazolothiolanion is suitably employed in the instant process. Although a molarequivalent of base is sufficient, the base serves a dual function. Itparticipates (1) in triazolothiol formation and (2) in theintramolecular displacement of halogen by thiol anion. In addition tothe lithium alkyls such as methyl lithium and butyl lithium, suitablebases include the alkoxides, amides, carbonates, hydrides and hydroxidesof the alkali metals. Among these are lithium ethoxide, potassiumt-butoxide, sodium methylate and the like. The carbonates and hydroxidesof lithium, sodium, potassium, cesium and rubidium can be used. Thepreferred bases which can be employed in the process of this inventionare lithium amide, sodium amide, potassium amide, sodium hydride,potassium hydride and the like.

The instant process is operated at a temperature range from about 60° C.to about 200° C. When the process is operated with the acylhydrazine andisothiocyanate compounds, an induction period at a temperature of about60° C. to about 100° C. for about 24 hours is employed to generate the1-acyl-4-(o-halophenyl)-3-thiosemicarbazide intermediate in situ. Afterthe induction period, a molar equivalent of the preferred sodium hydrideis added and the reaction is completed at a temperature of about 160°C., the boiling temperature of the preferred DMF solvent. When thethiosemicarbazide or triazolothiol compound is employed in the process,it is dissolved in the DMF, a molar equivalent of the preferred sodiumhydride is added and the reaction mixture is brought to refluxtemperature for a period of time sufficient to complete the reaction.Generally, the process is completed within 24 hours or less at atemperature between 60° C. and 100° C. Halogen displacement by thiolanion is influenced by the nature of the phenyl substituent groups. WhenR₂ and R₃ are electron donating groups such as C₁ -C₃ alkyl, halogendisplacement is retarded, thereby requiring extended reaction times.

All the triazolobenzothiazole compounds provided by this invention areuseful for the control of plant pathogens, particularly rice blast.

Illustrative of the 1-acyl-4-(o-halophenyl)-3-thiosemicarbazidecompounds which can be employed in the process of this invention are thefollowing:

4-(2-chlorophenyl)-1-formyl-3-thiosemicarbazide

1-acetyl-4-(2-chlorophenyl)-3-thiosemicarbazide

1-acetyl-4-(2-chloro-5-methylphenyl)-3-thiosemicarbazide

1-acetyl-4-(2-chloro-5-trifluoromethylphenyl)-3-thiosemicarbazide

1-acetyl-4-(2-chloro-4-methylphenyl)-3-thiosemicarbazide

1-acetyl-4-(2,5-dichlorophenyl)-3-thiosemicarbazide

4-(2-chlorophenyl)-1-heptanoyl-3-thiosemicarbazide

1-acetyl-4-(2-chloro-5-methoxyphenyl)-3-thiosemicarbazide

1-butyryl-4-(2-chloro-5-trifluoromethylphenyl)-3-thiosemicarbazide

4-(2-chlorophenyl)-1-cyclopropanecarbonyl-3-thiosemicarbazide

1-cyclopropanecarbonyl-4-(2,6-dichlorophenyl)-3-thiosemicarbazide

4-(2-chlorophenyl)-1-trifluoroacetyl-3-thiosemicarbazide

4-(2,6-dichloro-4-propoxyphenyl-1-trifluoroacetyl-3-thiosemicarbazide

4-(2-chloro-5-ethoxyphenyl)-1-propionyl-3-thiosemicarbazide

4-(2-bromo-6-fluoro-5-methylphenyl)-1-valeryl-3-thiosemicarbazide

1-isobutyryl-4-(2,4,6-trichlorophenyl)-3-thiosemicarbazide

4-(2-chloro-6-fluorophenyl)-1-decanoyl-3-thiosemicarbazide

4-(2-bromo-6-fluoro-5-methoxyphenyl)-1-butyryl-3-thiosemicarbazide

4-(2,6-dichloro-4-trifluorophenyl)-1-trifluoroacetyl-3-thiosemicarbazide

4-(2-chloro-6-fluoro-5-trifluoromethyl)-1-cyclopropanecarbonyl-3-thiosemicarbazide.

Illustrative of the4-(o-halophenyl)-5-substituted-1,2,4-triazole-3-thiol compounds whichcan be employed in the process of this invention are the following:

4-(2-chlorophenyl)-1,2,4-triazole-3-thiol

4-(2-chlorophenyl)-5-methyl-1,2,4-triazole-3-thiol

4-(2-chloro-5-trifluoromethylphenyl)-5-methyl-1,2,4-triazole-3-thiol

4-(2,4-dichlorophenyl)-5-methyl-1,2,4-triazole-3-thiol

4-(2-chloro-4-methylphenyl-5-methyl-1,2,4-triazole-3-thiol

4-(2,6-dichlorophenyl)-5-methyl-1,2,4-triazole-3-thiol

4-(2-chloro-5-methylphenyl)-5-methyl-1,2,4-triazole-3-thiol

4-(2-chloro-5-methoxyphenyl)-5-methyl-1,2,4-triazole-3-thiol

5-propyl-4-(2-chloro-5-trifluoromethylphenyl)-1,2,4-triazole-3-thiol

4-(2-chlorophenyl)-5-cyclopropyl-1,2,4-triazole-3-thiol

5-cyclopropyl-4-(2,6-dichlorophenyl)-1,2,4-triazole-3-thiol

4-(2-chlorophenyl-5-trifluoromethyl-1,2,4-triazole-3-thiol

4-(2,6-dichloro-4-propoxyphenyl)-5-trifluoromethyl-1,2,4-triazole-3-thiol

4-(2-chloro-5-ethoxyphenyl)-5-ethyl-1,2,4-triazole-3-thiol

4-(2-bromo-6-fluoro-5-methylphenyl)-5-butyl-1,2,4-triazole-3-thiol

5-isopropyl-4-(2,4,6-trichlorophenyl)-1,2,4-triazole-3-thiol

4-(2-chloro-6-fluorophenyl)-5-monyl-1,2,4-triazole-3-thiol

4-(2-bromo-6-fluoro-5-methoxyphenyl)-5-propyl-1,2,4-triazole-3-thiol

4-(2,6-dichloro-4-trifluoromethylphenyl)-5-trifluoromethyl-1,2,4-triazole-3-thiol

4-(2-chloro-6-fluoro-5-trifluoromethylphenyl)-5-cyclopropyl-1,2,4-triazole-3-thiol

Illustrative of the triazolobenzothiazole compounds provided by thisinvention are the following:

s-triazolo(3,4-b)benzothiazole

3-methyl-s-triazolo(3,4-b)benzothiazole

7-chloro-3-methyl-s-triazolo(3,4-b)benzothiazole

5-chloro-3-methyl-s-triazolo(3,4-b)benzothiazole

3,7-dimethyl-s-triazole(3,4-b)benzothiazole

3-heptyl-s-triazolo(3,4-b)benzothiazole

3-methyl-5-trifluoromethyl-s-triazolo(3,4-b)benzothiazole

3,6-dimethyl-s-triazolo(3,4-b)benzothiazole

6-methoxy-3-methyl-s-triazolo(3,4-b)benzothiazole

3-propyl-6-trifluoromethyl-s-triazolo(3,4-b)benzothiazole

3-cyclopropyl-s-triazolo(3,4-b)benzothiazole

5-chloro-3-cyclopropyl-s-triazolo(3,4-b)benzothiazole

3-trifluoromethyl-s-triazolo(3,4-b)benzothiazole

5-chloro-7-propoxy-3-trifluoromethyl-s-triazolo(3,4-b)benzothiazole

3-ethyl-6-ethoxy-s-triazolo(3,4-b)benzothiazole

5-fluoro-6-methyl-3-butyl-s-triazolo(3,4-b)benzothiazole

5,7-dichloro-3-isopropyl-s-triazolo(3,4-b)benzothiazole

5-fluoro-3-nonyl-s-triazolo(3,4-b)benzothiazole

5-fluoro-6-methoxy-3-propyl-s-triazolo(3,4-b)benzothiazole

5-chloro-3,7-bis(trifluoromethyl)-s-triazolo(3,4-b)benzothiazole

3-cyclopropyl-5-fluoro-6-trifluoromethyl-s-triazolobenzothiazole

The following examples further illustrate the preparation of thestarting materials, intermediates and compounds of our invention.

(I) Preparation of Thiosemicarbazides EXAMPLE 1 Preparation of1-formyl-4-(2-fluorophenyl)-3-thiosemicarbazide

Fifty grams (0.33 mole) of 2-fluorophenylisothiocyanate and 20 g. (0.33mole) of formylhydrazine were refluxed for 7 hours in 500 ml. oftetrahydrofuran (THF). The reaction mixture was allowed to cool and theinsoluble product was collected by filtration. The crude product waswashed with water, filtered and dried. The yield was 10 g. of1-formyl-4-(2-fluorophenyl)-3-thiosemicarbazide, mp. about 148°-149° C.

Analysis: C₈ H₈ FN₃ OS MW 213: Calc: C, 45.06; H, 3.78; N, 19.71. Found:C, 44.86; H, 3.55; N, 19.44.

EXAMPLE 2 Preparation of1-acetyl-4-(2-chloro-5-methylphenyl)-3-thiosemicarbazide

One tenth mole, 18.3 g., of 2-chloro-5-methylphenylisothiocyanate and11.0 g. (0.15 mole) of acetylhydrazine were refluxed for 7 hours in 500ml. of THF. After cooling, the insoluble product was collected byfiltration. The crude product was collected by filtration. The crudeproduct was washed with water, filtered and dried. The yield was 25 g.of 1-acetyl-4-(2-chloro-5-methylphenyl)-3-thiosemicarbazide, m.p. about145°-157° C.

Analysis: C₁₆ H₁₂ ClN₃ OS MW 257: Calc: C, 46.60; H, 4.69; N, 16.30.Found: C, 46.87; H, 4.92; N, 16.58.

EXAMPLES 3-7

The following 1-acetyl-4-substituted (o-halophenyl)-3-thiosemicarbazideswere prepared from acetylhydrazine and the appropriateo-halophenylisothiocyanates by the method of Example 2:

1-acetyl-4-(2-chlorophenyl)-3-thiosemicarbazide, m.p. about 152°-153° C.

Analysis: C₉ H₁₀ ClN₃ OS NW 243: Calc: C, 44.35; H, 4.14; N, 17.24.Found: C, 46.23; H, 4.28; N, 17.64.

1-acetyl-4-(2-chloro-4-methylphenyl)-3-thiosemicarbazide, m.p. about157°-159° C.

Analysis: C₁₀ H₁₂ ClN₃ SO MW 257: Calc: C, 46.60; H, 4.69; N, 16.30.Found: C, 46.37; H, 4.67; N, 16.50.

1-acetyl-4-(2,4-dichlorophenyl)-3-thiosemicarbazide, m.p. about 145°C.-147° C.

Analysis: C₉ H₉ Cl₂ N₃ SO MW 278: Calc: C, 38.86; H, 3.26; N, 15.11.Found: C, 39.02; H, 3.39; N, 15.02.

1-acetyl-4-(2,6-dichlorophenyl)-3-thiosemicarbazide, m.p. about157°-159° C.

Analysis: C₉ H₉ Cl₂ N₃ SO.H₂ O MW 296: Calc: C, 36.48; H, 3.71; N,14.19. Found: C, 36.49; H, 3.84; N, 14.67.

1-acetyl-4-(2-chloro-5-trifluoromethylphenyl)thiosemicarbazide, m.p.about 155°-156° C.

Analysis: C₁₀ H₉ ClF₃ N₃ SO MW 311: Calc: C, 38.53; H, 2.91; N, 13.48.Found: C, 38.86; H, 3.21; N, 13.83.

(II) Preparation of Triazoles EXAMPLE 8 Preparation of4-(2-fluorophenyl)-1,2,4-triazole-3-thiol

One and one-tenth grams (20 mmoles) of potassium hydroxide weredissolved in 50 ml. of water.1-Formyl-4-(2-fluorophenyl)thiosemicarbazide, 3.5 g. (16.5 mmoles), wasdissolved in the basic solution by warming on the steam bath untilsolution was completed. The heating was continued for 1 hour. The cooledreaction mixture was poured into a dilute solution of hydrochloric acid.The insoluble product was recovered from the acidic solution byfiltration. The product was washed with water, collected and dried. Theyield was 2.5 g. of 4-(2-fluorophenyl)-1,2,4-triazole-3-thiol, m.p.about 166°-167° C.

Analysis: C₈ H₆ FN₃ S MW 196: Calc: C, 49.22; H, 3.10; N, 21.53. Found:C, 49.09; H, 3.13; N, 21.37.

EXAMPLES 9-17

The following 4-(2-halophenyl)-1,2,4-triazole-3-thiols were preparedfrom the appropriately substituted thiosemicarbazides by cyclization inaqueous or alcoholic base by the method of Example 8:

4-(2-chlorophenyl)-1,2,4-triazole-3-thiol, m.p. about 195-196° C.

Analysis: C₈ H₆ ClN₃ S MW 211.5: Calc: C, 45.39; H, 2.96; N, 19.85.Found: C, 45,48; H, 3.10; N, 19.70.

4-(2-chlorophenyl)-5-methyl-1,2,4-triazole-3-thiol, m.p. about 217-219°C.

Analysis: C₉ H₈ ClN₃ S MW 225: Calc: C, 47.89; H, 3.57; N, 18.62. Found:C, 47.73; H, 3.64; N, 18.39.

4-(2,4-dichlorphenyl)-5-methyl-1,2,4-triazole-3-thiol, m.p. about248-253° C.

Analysis: C₉ H₉ Cl₂ N₃ S MW 260: Calc: C, 41.55; H, 2.71; N, 16.15.Found: C, 41.57; H, 2.81; N, 16.37.

4-(2-chloro-4-methylphenyl)-5-methyl-1,2,4-triazole-3-thiol, m.p. about243-244° C.

Analysis: C₁₀ H₁₀ ClN₃ S MW 239: Calc: C, 50.10; H, 4.20; N, 17.53.Found: C, 50.23; H, 4.24; N, 17.73.

4-(2-chloro-4-methylphenyl)-5-methyl-1,2,4-triazole-3-thiol, m.p. about229-231° C.

Analysis: C₁₀ H₁₀ ClN₃ S MW 239: Calc: C, 50.10; H, 4.20; N, 17.53.Found: C, 49.98; H, 4.27; N, 17.40.

4-(2,6-dichlorophenyl)-5-methyl-1,2,4-triazole-3-thiol, m.p. about240-242° C.

Analysis: C₉ H₇ CL₂ N₃ S MW 260: Calc: C, 41;55; H, 2.71; N, 16.15.Found: C, 41.32; H, 2.80; N, 15.98.

4-(2-chloro-6-methylphenyl)-1,2,4-triazole-3-thiol, m.p. about 237°C.-240° C.

Analysis: C₉ H₈ ClN₃ MW 225: Calc: C, 48.00; H, 3.55; N, 18.66. Found:C, 48.00; H, 3.32; N, 18.62.

4-(2-chloro-5-trifluoromethylphenyl)-5-methyl-1,2,4-triazole-3-thiol,m.p. about 208-209° C.

Analysis: C₁₀ H₇ ClF₃ NS MW 293: Calc: C, 40.90; H, 2.40; N, 14.31.Found: C, 40.95; H, 2.42; N, 14.27.

4-(2-chlorophenyl)-5-heptyl-1,2,4-triazole-3-thiol, m.p. about 150-157°C.

Analysis: C₁₅ H₂₀ ClN₃ S MW 309: Calc: C, 58.14; H, 6.51; N, 13.56.Found: C, 57.95; H, 6.33; N, 13.79.

(III) Preparation of Triazolobenzothiazoles EXAMPLE 18 Preparation ofs-triazolo[3,4-b]benzothiazole

Five grams (30.0 mmoles) of o-chlorophenylisothiocyanate were dissolvedin 50 ml. of dry DMF. A solution of 1.8 g. (30.0 mmoles) offormylhydrazine in 50 ml. of dry DMF was added dropwise rapidly to thestirred reaction mixture. The temperature of the reaction rose to about45° C. The temperature was maintained between 60° C. and 100° C. for 24hours. Thirty millimoles, 1.5 g., of sodium hydride as a 50% mineral oilsuspension was added to the reaction mixture. The reaction was completedby heating at reflux temperature (160° C.) for about 185 hours. Thecooled mixture was poured into water. The aqueous mixture was extractedwith n-hexane to remove mineral oil. The product was extracted withethyl acetate. The ethyl acetate extract was washed (water), dried(MgSO₄) and evaporated in vacuo to a residual oil. The oil was coveredwith dry ether and the product crystallized upon standing. The yield ofs-triazolo[3,4-b]benzothiazole, m.p. about 175-176° C., was 200 mg.

Analysis: C₈ H₅ N₃ S MW 175: Calc: C, 54.85; H, 2.88; N, 23.98. Found:C, 54.56; H, 2.94; N, 23.79.

EXAMPLE 19 Preparation of 3-methyl-s-triazolo(3,4-b)benzothiazole

Ten millimoles, 2.4 g., of 1-acetyl-4-(2-chlorophenyl)thiosemicarbazidewere dissolved in 50 ml. of dimethylformamide (DMF) under nitrogen. Oneequivalent, 0.5 g. (10 mmoles), of sodium hydride, as a 50% mineral oildispersion, was added to the reaction mixture. After refluxing for 126hours, the reaction mixture was poured into water. The aqueous mixturewas extracted with hexane to remove mineral oil followed by extractionwith chloroform. The chloroform extract was dried (MgSO₄) and evaporatedin vacuo to yield 400 mg. of 3-methyl-s-triazolo(3,4-b)benzothiazole.

Analysis: C₉ H₇ N₃ S MW 189: Calc: C, 57.12; H, 3.73; N, 22.21. Found:C, 56.84; H, 3.79; N, 22.23.

EXAMPLE 20 Preparation of7-chloro-3-methyl-s-triazolo[3,4-b]benzothiazole

Five grams (19 mmoles) of4-(2,4-dichlorophenyl)-5-methyl-1,2,4-triazole-3-thiol were dissolved in100 ml. of DMF. One gram (20 mmoles) of sodium hydride, as a 50% mineraloil dispersion, was added portionwise to the stirred reaction mixture.The mixture was refluxed for 24 hours and then poured into 600 ml. ofwater. The aqueous mixture was extracted with n-hexane to remove themineral oil. The aqueous phase was extracted with ethyl acetateovernight by means of a liquid-liquid extractor. The ethyl acetate wasdried (MgSO₄) and evaporated in vacuo to a residue. The residue waswashed with toluene and the crystalline product was collected byfiltration. The yield was 1.9 g. of7-chloro-3-methyl-s-triazolo[3,4-b]benzothiazole, m.p. about 186-188° C.A second crop, 1.6 g., m.p. about 185-188° C., was recovered from theaqueous phase.

Analysis: C₉ H₆ ClN₃ S MW 224: Calc: C, 48.33; H, 2.70; N, 18.79. Found:C, 48.32; H, 2.89; N, 18.96.

We claim:
 1. A 1-acyl-4-(o-halophenyl)-3-thiosemicarbazide compound ofthe formula ##STR12## wherein R is hydrogen, C₁ -C₁₁ alkyl, cyclopropylor trifluoromethyl;R₁ is hydrogen, bromo, chloro or fluoro; R₂ and R₃are independently hydrogen, C₁ -C₃ alkyl, C₁ -C₃ alkoxy, bromo, chloro,fluoro or trifluoromethyl with the limitation that at least one of R₂and R₃ is hydrogen; X is bromo, chloro or fluoro;subject to the furtherlimitation that when R₁ is halogen, R is other than hydrogen and R₂ ishydrogen.
 2. The compound of claim 1 which is1-formyl-4-(2-chlorophenyl)-3-thiosemicarbazide.
 3. The compound ofclaim 1 which is 1-acetyl-4-(2-chlorophenyl)-3-thiosemicarbazide.
 4. Thecompound of claim 1 which is1-acetyl-4-(2,4-dichlorophenyl)-3-thiosemicarbazide.
 5. The compound ofclaim 1 which is 1-acetyl-4-(2,6-dichlorophenyl)-3-thiosemicarbazide. 6.The compound of claim 1 which is1-acetyl-4-(2-chloro-5-methylphenyl)-3-thiosemicarbazide.
 7. Thecompound of claim 1 which is1-acetyl-4-(2-chloro-5-trifluoromethylphenyl)-3-thiosemicarbazide.